Structures of Sortase B from Staphylococcus aureus and Bacillus anthracis Reveal Catalytic Amino Acid Triad in the Active Site

Creators: Zhang, Rongguang; Wu, Ruiying; Joachimiak, Grazyna; Mazmanian, Sarkis K.; Missiakas, Dominique M.; Gornicki, Piotr; Schneewind, Olaf; Joachimiak, Andrzej

Abstract

Surface proteins attached by sortases to the cell wall envelope of bacterial pathogens play important roles during infection. Sorting and attachment of these proteins is directed by C-terminal signals. Sortase B of S. aureus recognizes a motif NPQTN, cleaves the polypeptide after the Thr residue, and attaches the protein to pentaglycine cross-bridges. Sortase B of B. anthracis is thought to recognize the NPKTG motif, and attaches surface proteins to m-diaminopimelic acid cross-bridges. We have determined crystal structure of sortase B from B. anthracis and S. aureus at 1.6 and 2.0 Å resolutions, respectively. These structures show a β-barrel fold with α-helical elements on its outside, a structure thus far exclusive to the sortase family. A putative active site located on the edge of the β-barrel is comprised of a Cys-His-Asp catalytic triad and presumably faces the bacterial cell surface. A putative binding site for the sorting signal is located nearby.

Additional Information

© 2004 Elsevier. Under an Elsevier user license. Received 29 April 2003, Revised 26 April 2004, Accepted 28 April 2004, Available online 13 July 2004. We thank all members of the SBC at ANL for their help conducting experiments and Lindy Keller for her help in preparation of this manuscript. This work was supported by grants from the National Institutes of Health, National Institute of General Medical Sciences to A.J. (GM62414), D.M.M. (GM58266), and O.S. (AI38897 and AI52474); by a University of Chicago-Argonne National Laboratory joint research grant under H.28 of the prime contract; by the U.S. Department of Energy, Office of Biological and Environmental Research, under contract W-31-109-Eng-38; and by the Regional Center of Excellence in Biodefense and Emerging Infectious Diseases (RCE) Program. The authors wish to acknowledge membership and support from the Region V (Great Lakes) RCE, award 1-U54-AI-057153 from the National Institutes of Allergy and Infectious Diseases. The submitted manuscript has been created by the University of Chicago as Operator of Argonne National Laboratory ("Argonne") under Contract No. W-31-109-ENG-38 with the U.S. Department of Energy. The U.S. Government retains for itself, and others acting on its behalf, a paid-up, nonexclusive, irrevocable worldwide license in said article to reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the Government. Accession Numbers: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes 1NG5 and 1RZ2).

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